Kit signaling pathway module

Stem cell factor (KIT ligand) binds and dimerizes the class III receptor tyrosine kinase KIT, whose autophosphorylated intracellular tyrosines recruit SH2-domain effectors (GRB2, PI3K p85, SHP2, Src-family kinases) that drive Ras-MAPK, PI3K-AKT, and STAT5 outputs controlling survival, proliferation, and migration of hematopoietic progenitors, mast cells, melanocytes, germ cells, and interstitial cells of Cajal.

Curated compact signaling-pathway module built to the same three-step template as the sibling receptor tyrosine kinase modules (pdgfr_signaling, egfr_signaling, fgfr_signaling): ligand engagement, phosphotyrosine effector recruitment, and downstream output. KIT is a class III receptor tyrosine kinase in the same PANTHER family (PTHR24416) as PDGFRA/PDGFRB, CSF1R, and FLT3; the module is kept separate from pdgfr_signaling because GO models Kit signaling as its own pathway term (GO:0038109) with its own PAINT node (PTN002814378) and its own ligand family (KITLG, family PTHR11574, rooted at Euteleostomi node PTN002611905, which carries PAINT IBDs for C:GO:0005886 and P:GO:0008284; the ligand participant uses GO:0005125 cytokine activity, a child of receptor ligand activity, rather than the receptor-specific binding term GO:0005173). Effector choice follows the reviews cited in evidence: GRB2 and PI3K p85 are the canonical SH2 adaptors recruited to phosphorylated KIT, SHP2 (PTPN11) is the KIT-associated phosphatase that couples to the Ras-ERK branch, and LYN is the Src-family kinase representative for the juxtamembrane phosphotyrosine docking site. Downstream outputs are limited to the three branches with GOA support on human KIT: positive regulation of MAPK cascade (IMP) and STAT activation (IMP, PMID:21135090) are experimentally grounded, while the PI3K-AKT branch (GO:0051897) is supported only by TAS (PMID:16129412); PLCG1 and other Ras-branch components are deliberately left to broader modules. PTN anchors are included only when the exemplar accession appears in an IBD seed row in interpro/panther; roles without local PAINT seeds remain grounded by verified UniProt exemplar accessions. UniProt protein names were taken verbatim from the UniProt REST API; PANTHER family labels from interpro/panther/panther.obo; PMIDs and titles were checked against PubMed. All nine human members (KIT, KITLG, GRB2, PIK3R1, PTPN11, LYN, SOS1, PIK3CA, STAT5A) now have curated gene reviews in genes/human, and gocams/index.tsv contains no KIT activity, so this module is not yet cross-checked against a production GO-CAM. Taxonomic scope: the class III RTK family (PTHR24416) is metazoan-deep, but the discrete Kit signaling pathway (GO:0038109) and the KIT-KITLG ligand-receptor pair are a bony-vertebrate feature (the IBD node carrying GO:0038109/GO:0046427, PTN002814378, is placed at NCBITaxon:117571 Euteleostomi); downstream effectors are ancient and shared across RTK pathways. As an alternate-species exemplar documenting teleost variation, the zebrafish co-orthologs kita (Q8JFR5, the sparse mutant) and kitlga (Q56JH6) were reviewed (genes/DANRE/kita, genes/DANRE/kitlga): they arose from the teleost whole-genome duplication and retain the ancestral pigmentation/hematopoiesis roles, while the paralogs kitb and kitlgb diverged and do not fully compensate, so zebrafish is not a one-to-one substitute for mammalian KIT/KITLG. Falcon integration (2026-09-25): Falcon findings are linked as evidence; the report's characterization of STAT5 as a conditional, lineage-dependent output is reflected in the output-step description and in the recorded knowledge gap. Automatically extracted open-question headings were not retained as knowledge_gap entries because they were not manually curated, and machine-generated Falcon citations remain curation support rather than adjudicated references.